Citations

ABSTRACT BACKGROUND AND PURPOSE The objective of this study was to longitudinally investigate the trajectory of change in 1 H MRS measurements in asymptomatic MAPT mutation carriers who became symptomatic during follow‐up, and to determine the time at which the neurochemical alterations accelerated during disease progression. METHODS We identified eight MAPT mutations carriers who transitioned from asymptomatic to symptomatic disease during follow‐up. All participants were longitudinally followed with an average of 7.75 years (range 4‐11 years) and underwent two or more single voxel 1 H MRS examinations from the posterior cingulate voxel, with a total of 60 examinations. The rate of longitudinal change for each metabolite was estimated using linear mixed models. A flex point model was used to estimate the flex time point of the change in slope. RESULTS The decrease in the NAA/mI ratio accelerated 2.09 years prior to symptom onset, and continued to decline. A similar trajectory was observed in the presumed glial marker mI/Cr ratio accelerating 1.86 years prior to symptom onset. CONCLUSIONS Our findings support the potential use of longitudinal 1 H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.

Abstract Humans vary considerably both in their baseline and activated immune phenotypes. We developed a user-friendly open-access web portal, ImmuneRegulation, that enables users to interactively explore immune regulatory elements that drive cell-type or cohort-specific gene expression levels. ImmuneRegulation currently provides the largest centrally integrated resource on human transcriptome regulation across whole blood and blood cell types, including (i) ∼43,000 genotyped individuals with associated gene expression data from ∼51,000 experiments, yielding genetic variant-gene expression associations on ∼220 million eQTLs; (ii) 14 million transcription factor (TF)-binding region hits extracted from 1945 ChIP-seq studies; and (iii) the latest GWAS catalog with 67,230 published variant-trait associations. Users can interactively explore associations between queried gene(s) and their regulators (cis-eQTLs, trans-eQTLs or TFs) across multiple cohorts and studies. These regulators may explain genotype-dependent gene expression variations and be critical in selecting the ideal cohorts or cell types for follow-up studies or in developing predictive models. Overall, ImmuneRegulation significantly lowers the barriers between complex immune regulation data and researchers who want rapid, intuitive and high-quality access to the effects of regulatory elements on gene expression in multiple studies to empower investigators in translating these rich data into biological insights and clinical applications, and is freely available at https://immuneregulation.mssm.edu.

Telomere length (TL) is associated with cardiovascular disease (CVD) and cancer. Obstructive sleep apnea (OSA) is also linked to higher risk of CVD and cancer, and to TL. We investigated the association between TL and risk of major adverse cardiac events (MACE) and cancer in OSA patients. We studied 210 individuals undergoing sleep-related studies between 2000 and 2007. Baseline characteristics and follow-up data (available in 164 subjects) were obtained from clinic records. Incidence rates were calculated for the entire group and by OSA status. Hazard ratios were calculated to estimate effects of OSA and TL on risk of MACE and cancer. In total, 32 individuals (20%) developed MACE and/or cancer during 12.7-year follow-up. The OSA group had a higher likelihood of cancer (16.0 vs. 4.9 events per 1000 person-years, P = 0.044) but no clear evidence of an elevated incidence of MACE (10.8 vs. 4.8 events per 1000 person-years, P = 0.293) compared to the non-OSA group. There was no association between TL and MACE- (HR = 1.01, 95% CI 0.78–1.28), or cancer-risk (HR = 1.18, 95% CI 0.96–1.43). Our study warrants further investigation of any modulating effect of OSA on TL and the risk of MACE and cancer.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Abstract Background: Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 play important roles in carcinogenesis, particularly for breast cancer. However, little is known about whether the IGF system influences histologic characteristics of normal glandular tissue and whether relationships vary by race. Lesser degrees of age-related terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. We examined the associations of IGF measures with TDLU involution of normal breast using standardized TDLU measures. Methods: Among 715 Caucasian and 283 African American (AA) women with normal breast tissue samples from the Komen Tissue Bank, serum concentrations of IGF-I and IGFBP-3 were quantified using enzyme-linked immunosorbent assay (ELISA). Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs (“TDLU count”) and acini/TDLU. Zero-inflated Poisson regression models with a robust variance estimator were used to estimate associations of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 molar ratio (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. We also tested for interactions by race using likelihood ratio tests. Results: AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p=0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p<0.0001); the differences persisted after adjustment for additional covariates including BMI and parity/age at first birth. Postmenopausal IGFBP-3 was inversely associated with TDLU count among both AA (RR T3vs.T1=0.49, 95% CI=0.28-0.84, p-trend=0.04) and Caucasian (RR T3vs.T1=0.63, 95% CI=0.41-0.99, p-trend=0.04) women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasians (OR T3vs.T1=1.33, 95% CI=1.01-1.31, p-trend=0.04) but not in AA (OR T3vs.T1=0.65, 95% CI=0.42-1.00, p-trend=0.05) women. There was no statistically significant interaction by race (p-interaction≥0.10). Conclusions: Our data suggest the potential role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast among both Caucasian and AA women. Citation Format: Hannah OH, Ruth M. Pfeiffer, Roni T. Falk, Hisani N. Horne, Jackie Xiang, Michael Pollak, Louise A. Brinton, Anna Maria V. Storniolo, Mark E. Sherman, Gretchen L. Gierach, Jonine D. Figueroa. Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution in Caucasian and African American women: The Susan G. Komen Tissue Bank [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A36.

Extensive mammographic density (MD), a well‐established breast cancer risk factor, is a radiological representation of stromal and epithelial breast tissue content. In studies conducted predominantly among Caucasian women, histologic measures of reduced terminal duct lobular unit (TDLU) involution have been correlated with extensive MD, but independently associated with breast cancer risk. We therefore examined associations between TDLU measures and MD among Chinese women, a low‐risk population but with high prevalence of dense breasts. Diagnostic pre‐treatment digital mammograms were obtained from 144 breast cancer cases at a tertiary hospital in Beijing and scored using the Breast Imaging Reporting and Data System (BI‐RADS) density classification. TDLU features were assessed using three standardized measures (count/100 mm2, span [μm], and acini count/TDLU) in benign tissues.Associations between each of TDLU measures and MD were examined using generalized linear models for TDLU count and span and polytomous logistic regression for acini count with adjustment for potential confounders stratified by age. Among women ≥50 years, 63% had dense breasts; cases with dense breasts (BI‐RADS, c‐d) had greater TDLU count (21.1 [SE = 2.70] vs. 9.0 [SE = 1.83]; p = 0.0004), longer span (480.6 μm [SE = 24.6] vs. 393.8 μm [SE = 31.8]; p = 0.03), and greater acini count (ORtrend = 16.1; 95%CI = 4.08–63.1; ptrend < 0.0001) compared to those with non‐dense breasts (BI‐RADS, a‐b). Among women <50 years, 91% had dense breasts, precluding our ability to detect associations. Our findings are consistent with previously reported associations between extensive MD and reduced TDLU involution, supporting the hypothesis that breast cancer risk associated with extensive MD may be related to the amount of “at‐risk” epithelium.

Background Sexual and gender minority individuals face numerous cancer‐related inequities, many of which appear to be underreported. However, to the best of the authors’ knowledge, no one has assessed rates of acquisition of sexual orientation and gender identity (SOGI) data within community oncology settings. Methods Community oncology practices that were part of the NCI Community Oncology Research Program (NCORP) network were asked whether they routinely collected SOGI information and coded this information in their electronic medical records. The proportion of practice groups reporting routine collection of sexual and/or gender minority information was calculated. Potential associations between the collection of SOGI information and practice group–level and state‐level characteristics (from Gallup poll data) were also provided. Results Twenty‐four percent of the responding NCORP practice groups reported routine collection of sexual orientation information, and 10% reported collection of gender identity information. Practices located in western regions of the United States, practices in states with higher proportions of sexual and gender minority–identifying individuals, and practices with lower proportions of non‐Hispanic patients were more likely to ask patients about sexual orientation and/or gender identity. Conclusions US oncology practices that participate in research do not frequently collect SOGI information from patients with cancer. Educational initiatives should inform oncology staff and providers about the importance of collecting gender identity and sexual orientation information to improve existent disparities faced by sexual and gender minority patients.

Objectives: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. Design: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. Subjects and Setting: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. Measurements and Main Results: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success. Conclusions: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.